A comic book series (based on the TV show) was published by DC Comics under the Johnny DC imprint, which lasted 6 issues, from 2006 to 2007. The show was designed primarily for young children.

The show was produced in a manner reminiscent of the Hanna-Barbera shows of the 1960s to the 1980s, from the sound effects down to the animation style (veteran Hanna-Barbera designer Iwao Takamoto served as a creative consultant). The series is rated TV-Y.

The show was close captioned by the National Captioning Institute like many of Warner Bros. Animation's shows at the time.

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As the planet Krypton is about to be destroyed, Superman's father Jor-El makes a ship and puts a white puppy named Krypto into it for a test flight to see if it is safe enough for interstellar travel. While aboard the ship, Krypto accidentally destroys several wires and causes the ship to put him into a deep sleep while it heads on to Earth.

Upon landing on Earth, Krypto is a fully grown dog, possessed of superpowers similar to those of Superman's (since all Kryptonian life-forms gain superpowers from exposure to a yellow sun, such as Earth's sun). Later, Krypto is adopted by Kevin Whitney, a 9-year-old boy, with whom Superman arranges for him to stay (as Superman himself is often too busy saving the world to take care of him). Krypto poses as an ordinary dog while living with Kevin's family, but adopts the secret identity of Krypto the Superdog for his superheroic deeds; Kevin is aware of Krypto's dual identity, but the rest of Kevin's family is not (excluding Kevin's spoiled cousin Bailey, however accidental). Kevin lives next door to Andrea, a girl who takes care of Streaky.

In the series, the various animals, including Krypto, all are capable of speaking to each other, but not to humans, except for Kevin and later Andrea (they are able to communicate with Krypto and the other animals thanks to a universal translator that they wear, known as an intergalactic communicator). The viewers can understand them, though, especially when Krypto and Streaky talk to the camera.

On December 15, 2006, the series ended. Reruns were shown on Kids' WB as part of the then-new CW network's E/I requirement, but stopped airing due to Kids' WB opting to use Cookie Jar Entertainment shows Will & Dewitt and Magi-Nation. Krypto was aired on Boomerang from February 5, 2007 to January 3, 2014.[2][3] The two-part holiday special, "Iguanukkah", aired on Cartoon Network, December 21, 2008 (as well as Christmas Eve and Christmas Day), as part of the all-day holiday specials marathon. It was shown on Boomerang.
Overseas, the show currently airs on Boomerang in Australia[4] and on France 3 (as part of Ludo) in France. The show began airing on Boomerang Latin America in 2014. In the UK & Ireland, the series upon starting aired on the CBBC Channel and for a short time on CBeebies, before later moving to Cartoonito. However, as of November 2017, it appears to be no longer broadcast on that channel. It has also aired on Cartoon Network in India, Pakistan, Bangladesh, Afghanistan, Iran and Tajikistan. Since September 2018 starting reruns in Tooncast in Latin America.